Identification of the cellular components involved in de novo immune hepatitis: a quantitative immunohistochemical analysis

Abstract

BackgroundDiagnosis of de novo immune hepatitis (dnIH) after liver transplantation relies on biopsy findings, with an abundance of plasma cells (PCs) in the inflammatory infiltrates a hallmark of the disease. Very little is known about what other types of immune cells exist in the infiltrates mainly located in the portal areas of the liver tissue.MethodsWe analyzed the composition of T cells, B cells, PCs, and macrophages in the liver biopsies of 12 patients with dnIH, 9 of them obtained at the time of diagnosis. For comparison, biopsies from 9 patients with chronic rejection (CR) were included in the study. The results were analyzed by a computer-assisted stereology quantification method.ResultsThe major components of the infiltrates in the portal areas were CD3+ T lymphocytes in both groups, with 36.6% in the dnIH group versus 49.4% in the CR group. CD20+ B lymphocytes represented 14.9% in the dnIH group and 29.1% in the CR group. Macrophage levels were very similar in the dnIH and CR group (19.7% versus 16.8%, respectively). PCs were much less represented in CR biopsies than those from the dnIH group (mean value of 4.7% versus 28.8%).ConclusionIn conclusion, the determination of a characteristic cellular profile could be an important tool for a more reliable diagnosis of dnIH, in support of the histological evaluation made by the pathologist, which in most cases is challenging. Recognition of this condition is crucial because it leads to graft failure if left untreated.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1440-8) contains supplementary material, which is available to authorized users.

Rethinking de novo immune hepatitis, an old concept for liver allograft rejection: Relevance of glutathione S-transferase T1 mismatch

“…We observed a predominance of T lymphocytes (mean 36.6%); followed by PCs (mean 28.8%), with 17% of them IgG4 + ; B cells (mean 14.9%); and macrophages (mean 19.7%) (Figure 4 ). This profile was very different to the one defined in a chronic rejection group included in the same study[ 58 ]. It remains to be confirmed whether the cellular composition in acute rejection biopsies would be useful to support diagnosis since HCV recurrence no longer has the same impact in the transplant community that as in the past.…”

“…Differential diagnosis of hepatic GvHD versus PC-rich rejection must be done in biopsy because histological features can only be analyzed in tissue to permit the differentiation of both processes. As it happens, the cellular composition of the inflammatory infiltrates in portal areas of HCT patient with PC-rich rejection was very similar to that of diagnostic biopsies of liver transplanted patients[ 58 ].…”

“…Direct visualization of the cell types with different markers and quantification of cells/mm 2 of tissue in diagnostic biopsies using computer-assisted system technology (newCAST) has proved to be an unbiased way to evaluate the situation directly in the organ and not only in peripheral blood (Figure 3 ). Very recent data allowed us to define a cellular profile characteristic of PC-rich rejection at the time of diagnosis[ 58 ]. We observed a predominance of T lymphocytes (mean 36.6%); followed by PCs (mean 28.8%), with 17% of them IgG4 + ; B cells (mean 14.9%); and macrophages (mean 19.7%) (Figure 4 ).…”

Computer-Assisted Definition of the Inflammatory Infiltrates in Patients With Different Categories of Banff Kidney Allograft Rejection

“…Serial sections of three-micrometer-thick formalin-fixed, paraffin-embedded tissue sections were handled as described (7). Incubation conditions for the primary antibodies are included in Supplementary Table 1.…”

“…The renal cortex was exhaustively evaluated by employing a stereological method that avoids observer subjectivity using new Computer-Assisted System Technology (newCAST™) by Visiopharm®. The newCAST™ stereology system was previously used in other transplant pathologies (7). To our knowledge, this work is the first application in human kidney transplantation.…”